Breast Pathology: Conventional Prognostic Markers

(1)

Chennai Breast Centre, Chennai, India

Breast cancer is a heterogeneous disease with a varied clinical outcome, underscoring the need for the use of reliable predictive and prognostic biomarkers. Prognostic markers help in estimating clinical outcome, regardless of treatment modality. Predictive markers are required for optimal therapeutic decision making and are indexes of the response of a patient to a specific therapeutic intervention. They help determine the sensitivity or resistance of a tumor to a particular therapy.

Conventional pathologic prognostic factors in breast cancer include the following.

Histological Subtype

There are five major histologic subtypes of invasive breast carcinoma: Invasive ductal carcinoma-no special type, invasive lobular, tubular, mucinous, and medullary carcinomas. The latter three are referred to as special histologic types as they are defined by uniform histologic features; these tumors are associated with a good clinical outcome. The prognosis of ductal carcinomas and lobular carcinomas varies from very good to very poor.

Tumor Size

Tumor size is a component of the TNM staging system and is directly related to prognosis. Increasing tumor size is independently associated with worsening survival. Pathological assessment of tumor size is the most accurate measurement. The tumor should be measured in three planes. The largest dimension is taken as the tumor size. When there is more than one lesion, the measurement of the largest tumor is taken as the tumor size for staging. When associated with DCIS, only the invasive component is taken for TNM assessment.

Tumors less than 15 mm have less likelihood of lymph nodal metastases and have a favorable clinical outcome.

Grade

Histologic grade is conventionally used to prognosticate ductal carcinoma. Grading can be carried out with satisfactory reproducibility, provided a strict protocol is followed. The Nottingham modification of Bloom and Richardson grading system with its strict protocol is highly reproducible and is widely followed. The grading involves assessment of the degree of architectural differentiation (tubule/acinar/ glandular formation), nuclear pleomorphism, and the frequency of mitosis in the tumor. Points are allocated to each category to obtain a total score. The Nottingham modification of Bloom and Richardson grading system categorizes tumors into low (3–5 points), intermediate (6 or 7 points), and high (8 or 9 points) grades.

Details of the Nottingham Modification of Bloom and Richardson Scoring System

Glandular/Acinar/Tubular Differentiation

All parts of the tumor are scanned and the assessment is done in the initial low-power scans of the tumor sections.

Score 1: >75 % of tumor area forming glands/tubules
Score 2: 10–75 % of tumor area forming glands/tubules
Score 3: <10 % of tumor area forming glands/tubules

Nuclear Pleomorphism

Tissue processing is an important factor in assessing nuclear pleomorphism. If sections are cut too thick, it may obscure the nuclear details.

Assessment of nuclear pleomorphism is the most subjective component of the grading system. The size and shape of the normal epithelial cells present in the breast tissue adjacent to the tumor is taken as a reference. Stromal lymphoid cells can be used as a reference if normal epithelial cells are not present in the sample.